Although the primary aim of diagnosing and treating musculoskeletal impairments is to restore functional three-dimensional (3D) movements, the majority of the quantitative diagnostic and evaluation tools available to the clinician have remained static and two dimensional. Thus, the current focus is to develop and ultimately validate a combined set of tools that will enable the accurate and precise measurement, analysis and visualization of 3D static and dynamic musculoskeletal anatomy (i.e., bone shape, skeletal kinematics, tendon and ligament strain, muscle force, and joint space). To accomplish this, the MR imaging and analysis capabilities already developed will be combined with highly accurate, imaging-based measurement and registration methodologies in order to non-invasively quantify complete joint anatomy and tissue dynamics during functional movements. Additionally, these tools will enable the quantification of 3D bone shape so that the effect that alterations joint and tissue dynamics have on bone shape can be quantified. Accomplishing the aims of the VFA initiative will fill an important knowledge gap that exists between the relationship of normal or impaired joint structure/function and the functional movement limitations associated with performing activities of daily living. In doing so, it will position the National Institutes of Health as an international leader in diagnostic evaluation of musculoskeletal impairments by advancing musculoskeletal diagnostic and evaluation tools from primarily static 2D tools to dynamic tools that can quantify 3D musculoskeletal function during dynamic tasks. Due to the natural tiered structure of this research, two primary paths are currently being pursued, one based using the VFA project in its current state to evaluate both normative and impaired joint kinematics and the other is the continued development of the VFA tools so that full musculoskeletal kinetics can be evaluated. The latter will require the development of methodologies for creating 3D digital images of loaded and moving joint tissues (bone, cartilage, and connective tissues) to reveal joint contact patterns and tissue loads. As part of the kinematics branch, the variability of bone shape and the sensitivity of defined joint posture (translation and rotation of one bone relative to another) to osteo-based coordinate system will be quantified. We intend to use these capabilities to document and evaluate the function of normal and impaired joint structures (e.g., Cerebral Palsy, Ehlos Danof syndrome, and patellar tracking syndrome) under simulated conditions experienced during activities of daily living. VFA Dynamic Tool Development Over the past year, we have maintained a research focus on developing the backbone for VFA and began to explore the issues surrounding the dynamic MR scanning of the musculoskeletal system. The key focal points for the algorithm development remained the image registration process along with continuing improvement in the integration algorithms. Fast-PC MRI provides 3D kinematics information for the bones of a joint (e.g., knee and ankle) as the subject brings this joint through a specified range of motion. Yet, this information cannot be readily applied to 3D models of the bones, which are created from static high-resolution scans of the joint. In order to apply the kinematics from the fast-PC MRI to the static models, the two image data sets have to be aligned (e.g., registered). Visualization is made possible by programs that have been written in-house using Matlabs scripting language. VFA Bone Shape Quantification Methodology Development The shape of a bone affects the dynamics of the musculoskeletal system by influencing the muscle length, tendon and ligament moment arms, skeletal kinematics and cartilage contact patterns. Variations in bone shape are symptomatic of orthopaedic disease and markers of human evolution. Thus,an understanding of bone shape and bone shape deformity is critical. However, quantifying the shape variation of bone surfaces extracted from volumetric image data is a complicated task. It requires careful alignment, also known as registration, an accurate representation of the bone shape, and the creation of a statistical normative bone shape model. To date no method has been developed for the combined quantification of global variation, in terms of orientation and translation, and the local shape variation for complicated shapes. Thus, the goal of this project is to develop and validate a single novel methodology that will both non-rigidly register (align) complicated shapes and quantify shape variations. A key advancement of this methodology will be that it will be able to work both on the global and local scale at the same time. This methodology will be used to define a normative femoral shape and describe the variation of that shape within a healthy population. In Vivo Normal and Impaired Knee Joint Function On the experimental side, a primary focus has been on evaluating the clinical applicability of the tools being developed by applying them to the study of knee joint function in children and adults diagnosed with Cerebral Palsy (n=20) Ehlers Danlos syndrome (n=10), stroke (n=2) and patellofemoral pain syndrome (n=30). The ultimate goal is to evaluate pre- and post-intervention joint function. We are in the process of analyzing the data acquired in order to quantify the various musculoskeletal parameters, such as joint kinematics, tendon strains, and tendon moment arms. As we complete the VFA toolbox, we should also be able to quantify forces in the quadriceps muscles, patellar tendon, the anterior cruciate ligament, and the cartilage during an extension/flexion cycle of the knee joint. The kinematics from these populations are being compared to our normative database. A major focus of this year has been on patellofemoral pain syndrome. A kinematics database of 34 impaired knees has been established in order to quantify the kinematics in this population and evaluate the effectiveness of McConnell taping. In Vivo Ankle Joint Function Currently we are developing the first normative database (n=32) for in vivo ankle joint kinematics, collected non-invasively during volitional movement. This dataset has provided new insights into the function of the rearfoot and will form the baseline for future studies investigating the clinical applicability of the VFA tools as they are applied to the ankle.